Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease with no known heritability, the cumulative incidence of
which has been placed at between 0.5 and 9.1% following acute pulmonary embolism [1,2]. A majority consensus on its development
has emerged predicated on the theory of disordered thrombus resolution following venous thromboembolism. This in part stems
from epidemiological data but is also based on studies implicating established clinical and laboratory factors, a central
theorem being that individuals respond differently to acute thrombotic insult.

Given traditional prothrombotic factors explain less than 10% of reported cases of CTEPH, we hypothesised a significant burden
of disease is accounted for by unidentified genetic factors. Using an unbiased approach of exome capture, we selected 20,
deeply phenotyped, young individuals (11 female) who had suffered large PE that subsequently developed haemodynamically confirmed
CTEPH despite anticoagulation. Individuals with known prothrombotic tendency and significant comorbidity were excluded. Selected
patients were White Caucasian origin.